Biodegradable and resorbable polymers play an ever increasing role in medicine, particularly because the bulk and molecular properties are amenable to manipulation to produce resorbable or partially resorbable medical products that alleviate morbidities associated with permanent implants. These polymers also generally enable pharmaceutical formulations to provide site-specific and sustained-release drug delivery. Biodegradable and resorbable polymers are also find use, for example, as coatings on medical devices, e.g., drug-eluting stents, catheters, surgical meshes and other devices, and can create another means for site-specific drug delivery. Further, these types of polymers can be formed into fully resorbable articles, with or without drugs, such as suture material, screws, device envelopes and coverings, medical grade pastes or putties, and other articles.
The myriad number of potential of medical applications requires biodegradable and resorbable polymers to have an equally diverse physical, chemical and biological properties. For biocompatibility purposes, the polymers must be suitable for use in animals and humans and thus lack toxicity under conditions of use. The degradation products of these polymers must also be non-toxic. Physically and chemically, the solubility, miscibility and release properties of the polymers need to accommodate varying drug elution and loading properties from different medical products. For example, anesthetic delivery may only be needed for several hours, the course of antibiotic delivery may be needed for 7-10 days, and the delivery of an immunogen may span several weeks or months. The requirements for timing of polymer degradation and resorption are also variable. In some applications, the polymer may need to remain at its site of action for at least a year to achieve complete healing and transfer of load. In other cases, such as with soft tissue, a much shorter duration (days, weeks or a few months) of polymer longevity may be desirable; whereas in other cases, if the polymer serves as a delivery vehicle, the actual time until the polymer resorbs may not be critical, so long as it resorbs within a reasonable, physiologically-relevant period.
The articles, coatings and formulations found in medical applications involving biodegradable and resorbable polymers are manufactured by many methods—using techniques as varied as spray-coating, molding, weaving, spinning, solvent casting, simple mixing and more—under a variety of conditions—high or low temperature, solvents, pressure, shear forces and more. Furthermore, if the particular application includes one or more drugs (including any biological molecules), these entities may be temperature sensitive, have limited solubility in the polymer or any solvents used during manufacture or have other incompatibilities with the manufacturing process for a given article, coating or formulation.
No matter the genesis, the diversity of product characteristics, whether of physical, chemical or biological origin, imposes a challenge to polymer selection and design on the polymer chemist.
Many classes of biodegradable and resorbable polymers are well known in the art. However, a surprising few are found in FDA approved medical products. No matter the reason that industry focuses its efforts on using very few polymers, some of those polymers retain inherent limitations, such as the polylactic acid and polyglycolic acid polymers which have been known to cause inflammatory reactions, or are not amenable to conditions of manufacture or medical use (lack thermostability or tensile strength). Consequently, a need exists to explore new classes of biocompatible, biodegradable and resorbable polymers for medical applications.
The present invention meets these needs by providing a new class of polymers based on dihydroxybenzoic acid (DHB) derivatives which are biodegradable and resorbable as well as on resorcinol derivatives. These biocompatible polymers allow the polymer chemist to select from an increasingly diverse array of polymers for medical applications.